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INTRODUCTION

In most women with epilepsy, it is necessary to continue antiepileptic drug (AED) treatment during pregnancy to reduce the risks caused by epileptic seizures for both mother and child.1,2,3 The risk of maternal death during pregnancy has been estimated to be ten times higher in women with epilepsy compared to the general population,4 possibly due to poor compliance with AED treatment and seizure occurrence. Seizure-related accidents and convulsive status epilepticus during pregnancy are associated with an increased risk of fetal death.5 Even brief generalized tonic–clonic seizures during pregnancy may have an unfavorable effect on cognitive outcome based on retrospective data,4 although this has not been confirmed prospectively.6,7

Foetal exposure to AEDs occurs in 0.3%–0.5% of all pregnancies; of them, 17%–47% are exposed to two or more drugs.8,9 Since both seizures during pregnancy and the medication needed to prevent seizures may have adverse foetal effects, the treatment of maternal epilepsy is a matter of balance by weighing advantages and disadvantages.

AEDs are freely transported across the placenta, and the foetal serum levels for most drugs are roughly the same as the maternal levels; valproate and possibly gabapentin seem to accumulate in the fetus.10,11 There is some evidence that infants born to women with epilepsy have low birth weight more commonly than infants of women with no chronic diseases.12,13 One minute Apgar scores may also be lower and the need for care in the neonatal ward is increased in the infants of mothers with epilepsy.9 These effects do not seem to be very strong and are not readily explained by pregnancy complications, exposure to specific AEDs, or seizures during pregnancy.9,12,14

STRUCTURAL AND FUNCTIONAL TERATOGENESIS

Structural teratogenesis resulting in malformations occurs during the first trimester of pregnancy. The vulnerable period for functional teratogenesis producing cognitive and behavioral disturbances covers the whole pregnancy as neuronal migration and organization are teratogen-sensitive processes continuing also in the second and third trimesters.15 Animal studies have demonstrated that AEDs have dose-dependent teratogenic effects. The doses required for functional deficits are generally lower than those producing structural anomalies.16

The prevalence of major malformations in the general population is approximately 2.2%–2.8% according to population-based studies.8,17 It is well established that prenatal exposure to AEDs increases the prevalence of major malformations in humans (Fig. 51–1).18 The magnitude of the risk is approximately two- to threefold for most monotherapies compared to the baseline rate. The most common malformations are the same that are common in the general population (e.g., heart defects and facial clefts). The highest relative risk in children of mothers with epilepsy has been observed in spina bifida and congenital anomalies of genital organs.17 Comparisons between different studies and pooling of ...